Streptococcus mutans, etiologic agent of dental caries, is divided into 7 serotypes. We have isolated and characterized antigens possessing determinants for serotypes a, b, c, and e. Also, we have found that several strains induce in rabbits anibodies able to react with human heart-tissue in vitro. Crude wall and membrane preparations from these organisms adsorb tissue-reactive antibodies from human acute rheumatic fever sera. Preliminary data indicate that S. mutans may contain heart-reactive antigens (HRA) in common with S. pyogenes, etiologic agent of rheumatic diseases. These findings warrant caution in the trial of proposed anti-caries vaccines. Presently, we are preparing both purified cell walls and membranes, the latter from mutanolysin-induced spheroplasts of S. mutans, in order to isolate streptococcal HRA's for purification and characterization by immunochemical and immunological means. Also, we shall attempt to determine the ultrastructural localization in human tissue of antibody binding sites. A senstitive technique for immunocytologic staining, horse-radish peroxidase, will be employed. The presence of common or distinct binding sites for the anti-streptococcal immunoglobulins (S. mutans vs. S. pyogenes) will be determined. Finally, the possible origin of binding sites will be studied as we attempt to link lipoteichoic acid-HRA complexes or acylated carbohydrate polymers to erythrocyte membranes.